Reactome | Cytosolic HIF1AN (FIH1) hydroxylates asparagine residues of Hypoxia-inducible Factor Alpha (HIF1A,HIF2A)

Cytosolic HIF1AN (FIH1) hydroxylates asparagine residues of Hypoxia-inducible Factor Alpha (HIF1A,HIF2A)

Stable Identifier

R-HSA-1234164

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Cytosolic HIF1AN (FIH1) hydroxylates asparagine residues of Hypoxia-inducible Factor Alpha (HIF1A,HIF2A)

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HIF1AN (FIH, FIH-1) forms a homodimer that hydroxylates an asparagine residue on HIF1A and HIF2A (Hewitson et al. 2002, Lando et al. 2002, Metzen et al. 2003, Koivunen et al. 2004, Lancaster et al. 2004). The hydroxylation of the asparagine interferes with the interaction between HIF1A/HIF2A and p300, a histone acetylase, and therefore inhibits the ability of HIF1A/2A to activate transcription of target genes (Lando et al. 2002). Because molecular oxygen is a substrate of the reaction, hypoxia is a negative regulator of this reaction and thereby increases transcriptional activation of target genes by HIF1A/2A.

Literature References

PubMed ID	Title	Journal	Year
11823643	Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch Whitelaw, ML, Peet, DJ, Gorman, JJ, Lando, D, Whelan, DA	Science	2002
15239670	Disruption of dimerization and substrate phosphorylation inhibit factor inhibiting hypoxia-inducible factor (FIH) activity Hewitson, KS, McDonough, MA, Aplin, RT, Lancaster, DE, Schofield, CJ, Pugh, CW, McNeill, LA, Ratcliffe, PJ	Biochem J	2004
12080085	FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor Whitelaw, ML, Peet, DJ, Gorman, JJ, Lando, D, Whelan, DA, Bruick, RK	Genes Dev	2002
12042299	Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family Gleadle, JM, Elkins, JM, Hewitson, KS, Bullock, AN, Riordan, MV, Pugh, CW, Welford, RW, Tian, YM, Bhattacharya, S, Oldham, NJ, Schofield, CJ, McNeill, LA, Ratcliffe, PJ	J Biol Chem	2002
12615973	Intracellular localisation of human HIF-1 alpha hydroxylases: implications for oxygen sensing Stengel, P, Klinger, M, Acker, H, Hellwig-Bürgel, T, Fandrey, J, Wotzlaw, C, Metzen, E, Berchner-Pfannschmidt, U, Huang, WQ, Marxsen, JH, Stolze, I, Jelkmann, W	J Cell Sci	2003
14701857	Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases Hirsilä, M, Günzler, V, Koivunen, P, Myllyharju, J, Kivirikko, KI	J Biol Chem	2004